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对人类和小鼠启动子中的组织特异性结构模式进行建模。

Modeling tissue-specific structural patterns in human and mouse promoters.

机构信息

Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.

出版信息

Nucleic Acids Res. 2010 Jan;38(1):17-25. doi: 10.1093/nar/gkp866. Epub 2009 Oct 22.

Abstract

Sets of genes expressed in the same tissue are believed to be under the regulation of a similar set of transcription factors, and can thus be assumed to contain similar structural patterns in their regulatory regions. Here we present a study of the structural patterns in promoters of genes expressed specifically in 26 human and 34 mouse tissues. For each tissue we constructed promoter structure models, taking into account presences of motifs, their positioning to the transcription start site, and pairwise positioning of motifs. We found that 35 out of 60 models (58%) were able to distinguish positive test promoter sequences from control promoter sequences with statistical significance. Models with high performance include those for liver, skeletal muscle, kidney and tongue. Many of the important structural patterns in these models involve transcription factors of known importance in the tissues in question and structural patterns tend to be conserved between human and mouse. In addition to that, promoter models for related tissues tend to have high inter-tissue performance, indicating that their promoters share common structural patterns. Together, these results illustrate the validity of our models, but also indicate that the promoter structures for some tissues are easier to model than those of others.

摘要

人们认为,在同一组织中表达的基因集合受到相似的转录因子调控,因此可以假定它们的调控区具有相似的结构模式。在这里,我们研究了在 26 个人类和 34 种老鼠组织中特异性表达的基因启动子中的结构模式。对于每种组织,我们构建了启动子结构模型,考虑了基序的存在、它们在转录起始位点的位置以及基序的成对位置。我们发现,在 60 个模型中有 35 个(58%)能够以统计学意义区分阳性测试启动子序列和对照启动子序列。性能较高的模型包括肝脏、骨骼肌、肾脏和舌模型。这些模型中的许多重要结构模式都涉及到在相关组织中具有重要作用的转录因子,并且结构模式在人类和老鼠之间趋于保守。此外,相关组织的启动子模型在组织间具有较高的性能,表明它们的启动子具有共同的结构模式。总的来说,这些结果说明了我们模型的有效性,但也表明某些组织的启动子结构比其他组织更容易建模。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdd3/2800225/31266f61db36/gkp866f1.jpg

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